tbuckley/cabot-search huggingface dataset:
John York Moore
Authors: David York Moore, Tim Robinson
Journal: BMJ (2022)

Mechanical properties of relaxed lower leg muscles were assessed by torque measurements during imposed constant velocity dorsiflexion-plantarflexion cycles. At low angular velocities, they exhibited an elastic and an energy-consuming, velocity-independent (plastic) resistance. In most patients with long-standing spasticity, both of these were enhanced. The results support the hypothesis of secondary structural changes of muscles in spasticity.
Ixazomib, lenalidomide and dexamethasone consolidation with randomized ixazomib or lenalidomide maintenance after autologous transplant in newly diagnosed multiple myeloma
Authors: Michael Slade, Thomas G. Martin, Nitya Nathwani, Mark A. Fiala, Michael P. Rettig, Feng Gao, Abhinav Deol, Francis K. Buadi, Jonathan L. Kaufman, Craig C. Hofmeister, Tara K. Gregory, Jesus Berdeja, Ajai Chari, Ashley Rosko, Ravi Vij
Journal: Leukemia (2022)
Ultrasmall, elementary and highly translational nanoparticle X-ray contrast media from amphiphilic iodinated statistical copolymers
Authors: Lu Su, Kellie S. Dalby, Hannah Luehmann, Sussana A. Elkassih, Sangho Cho, Xun He, Lisa Detering, Yen-Nan Lin, Nari Kang, Dennis A. Moore, Richard Laforest, Guorong Sun, Yongjian Liu, Karen L. Wooley
Journal: Acta Pharmaceutica Sinica B (2022)

To expand the single-dose duration over which noninvasive clinical and preclinical cancer imaging can be conducted with high sensitivity, and well-defined spatial and temporal resolutions, a facile strategy to prepare ultrasmall nanoparticulate X-ray contrast media (nano-XRCM) as dual-modality imaging agents for positron emission tomography (PET) and computed tomography (CT) has been established. Synthesized from controlled copolymerization of triiodobenzoyl ethyl acrylate and oligo(ethylene oxide) acrylate monomers, the amphiphilic statistical iodocopolymers (ICPs) could directly dissolve in water to afford thermodynamically stable solutions with high aqueous iodine concentrations (>140 mg iodine/mL water) and comparable viscosities to conventional small molecule XRCM. The formation of ultrasmall iodinated nanoparticles with hydrodynamic diameters of
Single CT colonography versus three rounds of faecal immunochemical test for population-based screening of colorectal cancer (SAVE): a randomised controlled trial
Authors: Lapo Sali, Leonardo Ventura, Mario Mascalchi, Massimo Falchini, Beatrice Mallardi, Francesca Carozzi, Stefano Milani, Marco Zappa, Grazia Grazzini, Paola Mantellini
Journal: The Lancet. Gastroenterology & hepatology (2022)
Impact of Prosthesis-Patient Mismatch After Transcatheter Aortic Valve Replacement
Authors: Michel Pompeu Sá, Xander Jacquemyn, Jef Van den Eynde, Panagiotis Tasoudis, Aleksander Dokollari, Gianluca Torregrossa, Serge Sicouri, Marie-Annick Clavel, Philippe Pibarot, Basel Ramlawi
Journal: JACC. Cardiovascular imaging (2022)
Unemployment and insecure housing are linked to less successful treatment for depression
Authors: Helen Saul, Deniz Gursul, Lauren Hoskin, Joshua Buckman
Journal: BMJ (2022)

The study Buckman JEJ, Saunders R, Stott J, et al. Socioeconomic indicators of treatment prognosis for adults with depression: a systematic review and individual patient data meta-analysis. JAMA Psychiatry 2022;79:5. To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/unemployment-insecure-housing-linked-less-successful-depression-treatment/
The Assessment of Severity in Patients with Coronary Artery Disease Through Coronary Angiotomography and Physical-Functional Assessment
Authors: Carlos José Oliveira de Matos
Journal: Clinical Cardiology and Cardiovascular Interventions (2022)

Background: The assessment of the coronary artery calcium score and the degree of coronary stenosis with the aim of tracking a higher risk for coronary events, when associated with an assessment of functional health, may indicate possible physical disabilities that will impact their quality of life. Design: Cross-sectional study. Methods: 208 patients underwent coronary artery calcium score quantification and were divided into absent (0), low (1-100), intermediate (101-400) and high / very high (&gt; 400), as well as the degree of coronary artery stenosis through percentage. Functional assessment was performed through the measure of functional independence, modified Katz index and Barthel index, and for physical capacity and the 6-minute walk test, with statistical analysis through analysis of variance. Results: The middle ages were 57±11,2 years and 61,5% were females. The most frequent risk factors were high blood pressure (78,4%) and family history to CAD (72,1%). The most common level was intermediate, 23,8%. The functionality showed a deficit of 19%; the distance travelled was 67,9% of the predicted distance, with differences observed between coronary arterial calcium score groups (p=0,03). The functionality was associated with the sedentary lifestyle (p=0,007) and dyspnea (p=0,008), while the physical capacity was associated with the dyspnea (p=0,03). Conclusions: Patients with coronary artery disease with a higher calcium score (&gt;400) had reduced physical capacity. Functionality showed that there was an association with a sedentary lifestyle and dyspnea.
Therapeutic Potential of Targeting Regulated Intramembrane Proteolysis Mechanisms of Voltage-Gated Ion Channel Subunits and Cell Adhesion Molecules
Authors: Samantha L. Hodges, Alexandra A. Bouza, Lori L. Isom
Journal: Pharmacological Reviews (2022)

Several integral membrane proteins undergo regulated intramembrane proteolysis (RIP), a tightly controlled process through which cells transmit information across and between intracellular compartments. RIP generates biologically active peptides by a series of proteolytic cleavage events carried out by two primary groups of enzymes: sheddases and intramembrane-cleaving proteases (iCLiPs). Following RIP, fragments of both pore-forming and non–pore-forming ion channel subunits, as well as immunoglobulin super family (IgSF) members, have been shown to translocate to the nucleus to function in transcriptional regulation. As an example, the voltage-gated sodium channel <i>β</i>1 subunit, which is also an IgSF-cell adhesion molecule (CAM), is a substrate for RIP. <i>β</i>1 RIP results in generation of a soluble intracellular domain, which can regulate gene expression in the nucleus. In this review, we discuss the proposed RIP mechanisms of voltage-gated sodium, potassium, and calcium channel subunits as well as the roles of their generated proteolytic products in the nucleus. We also discuss other RIP substrates that are cleaved by similar sheddases and iCLiPs, such as IgSF macromolecules, including CAMs, whose proteolytically generated fragments function in the nucleus. Importantly, dysfunctional RIP mechanisms are linked to human disease. Thus, we will also review how understanding RIP events and subsequent signaling processes involving ion channel subunits and IgSF proteins may lead to the discovery of novel therapeutic targets. <h3>Significance Statement</h3> Several ion channel subunits and immunoglobulin superfamily molecules have been identified as substrates of regulated intramembrane proteolysis (RIP). This signal transduction mechanism, which generates polypeptide fragments that translocate to the nucleus, is an important regulator of gene transcription. RIP may impact diseases of excitability, including epilepsy, cardiac arrhythmia, and sudden death syndromes. A thorough understanding of the role of RIP in gene regulation is critical as it may reveal novel therapeutic strategies for the treatment of previously intractable diseases.
Extensive Intravascular Leiomyomatosis with Cardiac Involvement, Clinicopathological and Imaging Characteristics: A Case Report
Authors: Vásquez-Ortiz Zuilma Yurith
Journal: Clinical Cardiology and Cardiovascular Interventions (2022)

Intracardiac masses are a rare differential diagnosis in patients who present heart failure symptoms, these are classified by many authors as neoplastic or non-neoplastic, dependent or not on the heart chambers. Being able to differentiate and classify intracardiac masses is very important because treatment and prognosis depend on it. Intravascular leiomyomatosis is one of the rarest tumors, characterized by direct overgrowth of a uterine leiomyoma through adjacent veins with an unusual growth pattern. To date, less than 300 cases have been reported, with proliferation to the heart chambers being even rarer. We present the case of a female who presented to the emergency department due to dyspnea and palpitations, during his approach, a mass from the inferior vena cava was found causing intermittent tricuspid obstruction. Later it was documented as coming directly from the uterus, diagnosing intravascular leiomyoma by pathology.
Racial Disparities in Ischemic Heart Disease
Authors: James C Blankenship
Journal: Clinical Cardiology and Cardiovascular Interventions (2022)

Ischemic heart disease is a leading cause of death for most racial and ethnic minorities and is estimated to be responsible for one in seven deaths in the United States. Black adults have the highest burden of cardiovascular disease. Despite significant advances in treatment of ischemic heart disease and an increased awareness of racial disparities, racial and ethnic minority groups remained disproportionately burdened with ischemic heart disease and experience higher mortality and rehospitalization rates compared to Whites. This review details racial disparities in different syndromes, treatments, and outcomes of ischemic heart disease and suggests strategies for reducing or eliminating these disparities.
Richard Matthew Dodds
Authors: Miles Witham
Journal: BMJ (2022)

<h3>Objective</h3> In this study, the presence and severity of external auditory canal exostoses (EACE) in a group of white water kayakers related to the duration and intensity of kayaking and the number of ear infections reported were identified. <h3>Design</h3> A community-based volunteer cross-sectional study was completed with 92 kayakers (69 men, 23 women; mean (SD) age 29.3 (8.72) years) and 65 control volunteers (37 men, 28 women; mean (SD) age 36.9 (14.9) years). After exclusions, 269 individual ears were examined (154 kayakers and 115 controls). Participants completed a questionnaire and underwent otoscopic examination. Main outcome measures were the presence and severity of EACE, the duration and frequency of kayaking and self-reported ear infections. Exclusion criteria included other cold-water exposure, known ear pathology or poor visualisation of the auditory canal. <h3>Results</h3> The findings demonstrated that 69.5% of kayaker ears and 1.7% of the control group were found to have EACE. Severity of EACE was significantly associated with the duration (p&lt;0.01) and frequency (p&lt;0.05) of kayaking with 90.6% of kayakers that had participated for more than 10 years having evidence of EACE. A significant relationship also existed between the number of self-reported ear infections and the severity of EACE (p&lt;0.01). <h3>Conclusion</h3> There is a positive relationship between the duration and frequency of white water kayaking and the presence and severity of EACE and associated ear infections.
The CD4+ T cell response to a commensal-derived epitope transitions from a tolerant to an inflammatory state in Crohn’s disease
Authors: Thomas K. Pedersen, Eric M. Brown, Damian R. Plichta, Joachim Johansen, Shaina W. Twardus, Toni M. Delorey, Helena Lau, Hera Vlamakis, James J. Moon, Ramnik J. Xavier, Daniel B. Graham
Journal: Immunity (2022)
A self-sustaining layer of early-life-origin B cells drives steady-state IgA responses in the adult gut
Authors: Stefano Vergani, Konjit Getachew Muleta, Clément Da Silva, Alexander Doyle, Trine Ahn Kristiansen, Selene Sodini, Niklas Krausse, Giorgia Montano, Knut Kotarsky, Joy Nakawesi, Hugo Åkerstrand, Stijn Vanhee, Sneh Lata Gupta, David Bryder, William Winston Agace, Katharina Lahl, Joan Yuan
Journal: Immunity (2022)

The adult immune system consists of cells that emerged at various times during ontogeny. We aimed to define the relationship between developmental origin and composition of the adult B cell pool during unperturbed hematopoiesis. Lineage tracing stratified murine adult B cells based on the timing of output, revealing that a substantial portion originated within a restricted neonatal window. In addition to B-1a cells, early-life time-stamped B cells included clonally interrelated IgA plasma cells in the gut and bone marrow. These were actively maintained by B cell memory within gut chronic germinal centers and contained commensal microbiota reactivity. Neonatal rotavirus infection recruited recurrent IgA clones that were distinct from those arising by infection with the same antigen in adults. Finally, gut IgA plasma cells arose from the same hematopoietic progenitors as B-1a cells during ontogeny. Thus, a complex layer of neonatally imprinted B cells confer unique antibody responses later in life.
Azathioprine therapy induces selective NK cell depletion and IFN-γ deficiency predisposing to herpesvirus reactivation
Authors: Florian Ingelfinger, Colin Sparano, David Bamert, David Reyes-Leiva, Aakriti Sethi, Lukas Rindlisbacher, Pascale Zwicky, Stefanie Kreutmair, Corinne C. Widmer, Sarah Mundt, Elena Cortés-Vicente, Sonia Tugues, Burkhard Becher, Bettina Schreiner
Journal: Journal of Allergy and Clinical Immunology (2022)
Measurement properties for muscle strength tests following anterior cruciate ligament and/or meniscus injury: What tests to use and where do we need to go? A systematic review with meta-analyses for the OPTIKNEE consensus
Authors: Anouk P Urhausen, Bjørnar Berg, Britt Elin Øiestad, Jackie L Whittaker, Adam G Culvenor, Kay M Crossley, Carsten B Juhl, May Arna Risberg
Journal: British Journal of Sports Medicine (2022)

Critically appraise and summarise the measurement properties of knee muscle strength tests after anterior cruciate ligament (ACL) and/or meniscus injury using the COnsensus-based Standards for the selection of health Measurement INstruments Risk of Bias checklist.Systematic review with meta-analyses. The modified Grading of Recommendations Assessment, Development and Evaluation-guided assessment of evidence quality.Medline, Embase, CINAHL and SPORTSDiscus searched from inception to 5 May 2022.Studies evaluating knee extensor or flexor strength test reliability, measurement error, validity, responsiveness or interpretability in individuals with ACL and/or meniscus injuries with a mean injury age of ≤30 years.Thirty-six studies were included involving 31 different muscle strength tests (mode and equipment) in individuals following an ACL injury and/or an isolated meniscus injury. Strength tests were assessed for reliability (n=8), measurement error (n=7), construct validity (n=27) and criterion validity (n=7). Isokinetic concentric extensor and flexor strength tests were the best rated with sufficient intrarater reliability (very low evidence quality) and construct validity (moderate evidence quality). Isotonic extensor and flexor strength tests showed sufficient criterion validity, while isometric extensor strength tests had insufficient construct and criterion validity (high evidence quality).Knee extensor and flexor strength tests of individuals with ACL and/or meniscus injury lack evidence supporting their measurement properties. There is an urgent need for high-quality studies on these measurement properties. Until then, isokinetic concentric strength tests are most recommended, with isotonic strength tests a good alternative.
Dietary Fat Composition Affects Hepatic Angiogenesis and Lymphangiogenesis in Hepatitis C Virus Core Gene Transgenic Mice
Authors: Pan Diao, Yaping Wang, Fangping Jia, Xiaojing Wang, Xiao Hu, Takefumi Kimura, Yoshiko Sato, Kyoji Moriya, Kazuhiko Koike, Jun Nakayama, Naoki Tanaka
Journal: Liver Cancer (2022)

Previous research has demonstrated that an isocaloric diet rich in trans-fatty acid (TFA), saturated fatty acid (SFA), and cholesterol (Chol) promoted steatosis-derived hepatic tumorigenesis in hepatitis C virus core gene transgenic (HCVcpTg) mice in different manners. Growth factor signaling and ensuing angiogenesis/lymphangiogenesis are key factors in hepatic tumorigenesis that have become recent therapeutic targets for hepatocellular carcinoma. However, the influence of dietary fat composition on these factors remains unclear. This study investigated whether the type of dietary fat would have a specific impact on hepatic angiogenesis/lymphangiogenesis in HCVcpTg mice.Male HCVcpTg mice were treated with a control diet, an isocaloric diet containing 1.5% cholesterol (Chol diet), or a diet replacing soybean oil with hydrogenated coconut oil (SFA diet) for a period of 15 months or with shortening (TFA diet) for 5 months. The degree of angiogenesis/lymphangiogenesis and the expression of growth factors, including fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF), were evaluated in non-tumorous liver tissues using quantitative mRNA measurement, immunoblot analysis, and immunohistochemistry.Long-term feeding of SFA and TFA diets to HCVcpTg mice increased the expressions of vascular endothelial cell indicators, such as CD31 and TEK receptor tyrosine kinase, in addition to lymphatic vessel endothelial hyaluronan receptor 1, indicating that angiogenesis/lymphangiogenesis were upregulated only by these fatty acid-enriched diets. This promoting effect correlated with elevated VEGF-C and FGF receptor 2 and 3 levels in the liver. c-Jun N-terminal kinase (JNK) and hypoxia-inducible factor (HIF) 1α, both key regulators of VEGF-C expression, were enhanced in the SFA- and TFA-rich diet groups as well. The Chol diet significantly increased the expressions of such growth factors as FGF2 and PDGF subunit B, without any detectable impact on angiogenesis/lymphangiogenesis.This study revealed that diets rich in SFA and TFA, but not Chol, might stimulate hepatic angiogenesis/lymphangiogenesis mainly through the JNK-HIF1α-VEGF-C axis. Our observations indicate the importance of dietary fat species for preventing hepatic tumorigenesis.
Personalized neoantigen vaccine combined with PD-1 blockade increases CD8<sup>+</sup> tissue-resident memory T-cell infiltration in preclinical hepatocellular carcinoma models
Authors: Hengkai Chen, Zhenli Li, Liman Qiu, Xiuqing Dong, Geng Chen, Yingjun Shi, Linsheng Cai, Wenhan Liu, Honghao Ye, Yang Zhou, Jiahe Ouyang, Zhixiong Cai, Xiaolong Liu
Journal: Journal for ImmunoTherapy of Cancer (2022)

Personalized neoantigen vaccine could induce a robust antitumor immune response in multiple cancers, whose efficacy could be further enhanced by combining with programmed cell death 1 blockade (α-PD-1). However, the corresponding immune response and synergistic mechanisms remain largely unclear. Here, we aimed to develop clinically available combinational therapeutic strategy and further explore its potential antitumor mechanisms in hepatocellular carcinoma (HCC).Neoantigen peptide vaccine (NeoVAC) for murine HCC cell line Hepa1-6 was developed and optimized by neoantigen screening and adjuvant optimization. Then the synergistic efficacy and related molecular mechanisms of NeoVAC combined with α-PD-1 in HCC were evaluated by orthotopic HCC mouse model, single-cell RNA sequencing, tetramer flow cytometry, immunofluorescence, etc. The tumor-killing capacity of CD8+ tissue-resident memory T cells (CD8+ TRMs) was assessed by orthotopic HCC mouse model, and autologous patient-derived cells.NeoVAC, which consisted of seven high immunogenic neoantigen peptides and clinical-grade Poly(I:C), could generate a strong antitumor immune response in HCC mouse models. Significantly, its efficacy could be further improved by combining with α-PD-1, with 80% of durable tumor regression and long-term immune memory in orthotopic HCC models. Moreover, in-depth analysis of the tumor immune microenvironment showed that the percentage of CD8+ TRMs was remarkedly increased in NeoVAC plus α-PD-1 treatment group, and positively associated with the antitumor efficacy. In vitro and in vivo T-cell cytotoxicity assay further confirmed the strong tumor-killing capacity of CD8+ TRMs sorting from orthotopic mouse HCC or patient's HCC tissue.This study showed that NeoVAC plus α-PD-1 could induce a strong antitumor response and long-term tumor-specific immune memory in HCC by increasing CD8+ TRMs infiltration, which might serve as a potential immune-therapeutic target for HCC.
Oral beclomethasone dipropionate is an effective treatment for immune checkpoint inhibitor induced colitis
Authors: James L Alexander, Hajir Ibraheim, Camellia Richards, Ben Shum, Polychronis Pavlidis, Nikki Hunter, Julian P Teare, Andrew Wotherspoon, Andrew Furness, Samra Turajlic, Lisa Pickering, James Larkin, Ally Speight, Sophie Papa, Nick Powell
Journal: Journal for ImmunoTherapy of Cancer (2022)

Introduction Systemic corticosteroids are the mainstay of treatment for immune checkpoint inhibitor induced (CPI) colitis but are associated with complications including life-threatening infection. The topically acting oral corticosteroid beclomethasone dipropionate (BD) is an effective treatment for mild to moderate flares of ulcerative colitis, and has fewer side effects than systemic corticosteroids. We hypothesized that BD would be an effective treatment for CPI-induced colitis. Methods We performed a retrospective analysis of all patients who started BD for CPI-induced colitis at three UK cancer centers between November 2017 and October 2020. All patients underwent endoscopic assessment and biopsy. The initial regimen of BD was 5 mg once daily for 28 days. Data were collected from electronic patient records. Clinical outcomes were assessed at 28 days after initiation of treatment. Results Twenty-two patients (14 male) with a median age of 64 (range 45–84) with CPI-induced colitis were treated with BD. At baseline, the median number of loose stools in a 24-hour period was six (common terminology criteria for adverse events, CTCAE grade diarrhea=2). Thirteen patients (59%) were dependent on systemic corticosteroids prior to starting BD. Baseline sigmoidoscopy showed moderate inflammation (Mayo Endoscopic Score (MES) = 2) in two patients (9%), mild inflammation (MES=1) in nine patients (41%) and normal findings (MES=0) in eleven patients (50%). Twenty patients (91%) had histopathological features of inflammation. All 22 patients (100%) had a clinical response to BD and 21 (95%) achieved clinical remission with a return to baseline stool frequency (CTCAE diarrhea=0). Ten patients (45%) had symptomatic relapse on cessation of BD, half within 7 days of stopping. All patients recaptured response on restarting BD. No adverse events were reported in patients treated with BD. Conclusions Topical BD represents an appealing alternative option to systemic immunosuppressive treatments to treat colonic inflammation. In this study, BD was effective and safe at inducing remission in CPI-induced colitis, which was refractory to systemic corticosteroids. Further randomized studies are needed to confirm these findings and determine the optimum dosing regimen.